In this proposal we plan to follow two different strategies for immunocontraception in males. Both of these strategies are aimed at developing an effective immunocontraceptive in the absence of undesirable immune responses such as immune orchitis or other inflammation in the male reproductive tract. Both active and passive immunizations are proposed. (1) For active immunizations we will use a peptide that contains a single antibody-binding site (epitope) that is only present on the surface of post-testicular sperm. This epitope is created by proteolytic processing of the sperm-specific surface protein, PH-30, during epididymal maturation. The epitope is absent from other regions of the male reproductive tract including the testis and epididymal epithelium. A monoclonal antibody (MAb) to the epitope blocks fertilization. (2) The second approach, designed to avoid adverse cell-mediated immune responses, will be passive immunization with syngeneic MAbs to the PH-29 or PH-30 proteins.